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The Central Response to Ovarian Carcinoma Simulates the Response to Sepsis

1998; Elsevier BV; Volume: 75; Issue: 2 Linguagem: Inglês

10.1006/jsre.1997.5183

1095-8673

Linda F. Carson, Sabita Roy, Kelly Cain, Richard Charboneau, Stanley DeTurris, S Ramakrishin, Roderick A. Barke,

Neonatal Respiratory Health Research

Background: Animal models of stress and sepsis demonstrate increased hypophyseal gene expression of the transcription factorc-fosand the cytokines interleukin-1 and interleukin-6. Chronic central nervous system exposure to interleukin-1 results in hypermetabolism, accelerated nitrogen loss, anorexia, and cachexia. We test the hypothesis that the host response to ovarian carcinoma recapitulates the host response to sepsis regarding the elaboration of the transcription factors and cytokines in the central nervous system, liver, and lung. Materials and methods: Nude mice were seeded intraperitoneally with either ovarian carcinoma (MA-148) or vehicle. The animal subjects were observed for 5 weeks and sacrificed for brain, pituitary, lung, and liver mRNA. We studied the mRNA accumulation of the transcription factorsc-fos, c-jun,and C/EBPα and the cytokines interleukin-1 and interleukin-6 using reverse-transcriptase polymerase chain reaction. Results: Compared with the control, ovarian carcinoma in the mouse model resulted in the following: (1) Pituitaryc-fosandc-junmRNA increased 3-fold (P= 0.012) and 6-fold (P< 0.001), respectively; (2) pituitary IL-1 and IL-6 mRNA increased 4-fold (P< 0.001) and 8-fold (P= 0.037), respectively; (3) liverc-fosmRNA increased >8-fold (P< 0.001); and (4) lung C/EBPα mRNA decreased greater than 10-fold (P< 0.001). Conclusions: We conclude that the host response to ovarian carcinoma in this animal model recapitulates many aspects of the host response to bacterial sepsis especially concerning pituitary gene expression. These data suggest that, as in sepsis, a hypothalamic–hypophyseal-mediated cytokine response in ovarian carcinoma may result in hypermetabolism, accelerated nitrogen loss, anorexia, and cachexia.